Category: Etiology

Is chronic fatigue syndrome caused by a rare brain infection of a common, normally benign virus?

Abstract:

Chronic fatigue syndrome (CFS) is a disabling disease of unknown aetiology. A variety of factors have been suggested as possible causes. Although the symptoms and clinical findings are heterogeneous, the syndrome is sufficiently distinct, at least in relation to the more obvious cases, that a common explanation seems likely. In this paper, it is proposed that the disease is caused by a ubiquitous, but normally benign virus, e.g., one of the circoviruses.

Circoviruses are chronically present in a majority of people, but are rarely tested for diagnostically. Normally these viruses do not penetrate the blood-brain barrier, but exceptions have been reported, and related viruses cause disease in the central nervous system of animals.

The flu-like illness that often precedes the onset of CFS may either suppress immune function, causing an increased viremia, and/or lower the blood-brain barrier. In both cases the result may be that a virus already present in the blood enters the brain. It is well known that zoonotic viruses typically are more malignant than viruses with a long history of host-virus evolution. Similarly, a virus reaching an unfamiliar organ may cause particular problems.

 

Source: Grinde B. Is chronic fatigue syndrome caused by a rare brain infection of a common, normally benign virus? Med Hypotheses. 2008 Aug;71(2):270-4. doi: 10.1016/j.mehy.2008.03.014. Epub 2008 Apr 25. https://www.ncbi.nlm.nih.gov/pubmed/18440157

 

Etiology of chronic fatigue syndrome: testing popular hypotheses using a national birth cohort study

Abstract:

OBJECTIVE: To review the etiology of chronic fatigue syndrome (CFS) and test hypotheses relating to immune system dysfunction, physical deconditioning, exercise avoidance, and childhood illness experiences, using a large prospective birth cohort.

METHODS: A total of 4779 participants from the Medical Research Council’s National Survey of Health and Development were prospectively followed for the first 53 years of their life with >20 separate data collections. Information was collected on childhood and parental health, atopic illness, levels of physical activity, fatigue, and participant’s weight and height at multiple time points. CFS was identified through self-report during a semistructured interview at age 53 years with additional case notes review.

RESULTS: Of 2983 participants assessed at age 53 years, 34 (1.1%, 95% Confidence Interval 0.8-1.5) reported a diagnosis of CFS. Those who reported CFS were no more likely to have suffered from childhood illness or atopy. Increased levels of exercise throughout childhood and early adult life and a lower body mass index were associated with an increased risk of later CFS. Participants who later reported CFS continued to exercise more frequently even after they began to experience early symptoms of fatigue.

CONCLUSIONS: Individuals who exercise frequently are more likely to report a diagnosis of CFS in later life. This may be due to the direct effects of this behavior or associated personality factors. Continuing to be active despite increasing fatigue may be a crucial step in the development of CFS.

 

Source: Harvey SB, Wadsworth M, Wessely S, Hotopf M. Etiology of chronic fatigue syndrome: testing popular hypotheses using a national birth cohort study. Psychosom Med. 2008 May;70(4):488-95. doi: 10.1097/PSY.0b013e31816a8dbc. Epub 2008 Mar 31. https://www.ncbi.nlm.nih.gov/pubmed/18378866

 

Chronic fatigue syndrome is associated with chronic enterovirus infection of the stomach

Abstract:

BACKGROUND AND AIMS: The aetiology for chronic fatigue syndrome (CFS) remains elusive although enteroviruses have been implicated as one of the causes by a number of studies. Since most CFS patients have persistent or intermittent gastrointestinal (GI) symptoms, the presence of viral capsid protein 1 (VP1), enterovirus (EV) RNA and culturable virus in the stomach biopsy specimens of patients with CFS was evaluated.

METHODS: 165 consecutive patients with CFS underwent upper GI endoscopies and antrum biopsies. Immunoperoxidase staining was performed using EV-specific monoclonal antibody (mAb) or a control mAb specific for cytomegalovirus (CMV). RT-PCR ELISA was performed on RNA extracted from paraffin sections or samples preserved in RNA later. Biopsies from normal stomach and other gastric diseases served as controls. 75 samples were cultured for EV.

RESULTS: 135/165 (82%) biopsies stained positive for VP1 within parietal cells, whereas 7/34 (20%) of the controls stained positive (p< or =0.001). CMV mAb failed to stain any of the biopsy specimens. Biopsies taken from six patients at the onset of the CFS/abdominal symptoms, and 2-8 years later showed positive staining in the paired specimens. EV RNA was detected in 9/24 (37%) paraffin-embedded biopsy samples; 1/21 controls had detectable EV RNA (p<0.01); 1/3 patients had detectable EV RNA from two samples taken 4 years apart; 5 patient samples showed transient growth of non-cytopathic enteroviruses.

CONCLUSION: Enterovirus VP1, RNA and non-cytopathic viruses were detected in the stomach biopsy specimens of CFS patients with chronic abdominal complaints. A significant subset of CFS patients may have a chronic, disseminated, non-cytolytic form of enteroviral infection, which could be diagnosed by stomach biopsy.

Comment in: Enterovirus infection of the stomach in chronic fatigue syndrome/myalgic encephalomyelitis. [J Clin Pathol. 2008]

 

Source: Chia JK, Chia AY. Chronic fatigue syndrome is associated with chronic enterovirus infection of the stomach. J Clin Pathol. 2008 Jan;61(1):43-8. Epub 2007 Sep 13. https://www.ncbi.nlm.nih.gov/pubmed/17872383

 

Increased serum IgA and IgM against LPS of enterobacteria in chronic fatigue syndrome (CFS): indication for the involvement of gram-negative enterobacteria in the etiology of CFS and for the presence of an increased gut-intestinal permeability

Abstract:

There is now evidence that chronic fatigue syndrome (CFS) is accompanied by immune disorders and by increased oxidative stress. The present study has been designed in order to examine the serum concentrations of IgA and IgM to LPS of gram-negative enterobacteria, i.e. Hafnia alvei; Pseudomonas aeruginosa, Morganella morganii, Proteus mirabilis, Pseudomonas putida, Citrobacter koseri, and Klebsiella pneumoniae in CFS patients, patients with partial CFS and normal controls.

We found that the prevalences and median values for serum IgA against the LPS of enterobacteria are significantly greater in patients with CFS than in normal volunteers and patients with partial CFS. Serum IgA levels were significantly correlated to the severity of illness, as measured by the FibroFatigue scale and to symptoms, such as irritable bowel, muscular tension, fatigue, concentration difficulties, and failing memory.

The results show that enterobacteria are involved in the etiology of CFS and that an increased gut-intestinal permeability has caused an immune response to the LPS of gram-negative enterobacteria. It is suggested that all patients with CFS should be checked by means of the IgA panel used in the present study and accordingly should be treated for increased gut permeability.

 

Source: Maes M, Mihaylova I, Leunis JC. Increased serum IgA and IgM against LPS of enterobacteria in chronic fatigue syndrome (CFS): indication for the involvement of gram-negative enterobacteria in the etiology of CFS and for the presence of an increased gut-intestinal permeability. J Affect Disord. 2007 Apr;99(1-3):237-40. Epub 2006 Sep 27. https://www.ncbi.nlm.nih.gov/pubmed/17007934

 

Multiple chemical sensitivity in sick-building syndrome

Abstract:

The sick building syndrome includes irritation of the eyes and the respiratory tract neurotoxicity affectation and skin problems, which can occur in individuals under improperly ventilated buildings. Poor air quality, as shown in CO2 atmospheric levels of more than 1,000 ppm, results in a pathological exposure to biological and chemical products. We present a work-related case of multiple chemical hypersensitivity from a dialysis unit that had no air renewal. This person, who was summitted to continuous exposure despite having taken corrective measures in the ventilation, developed chronic fatigue syndrome. An acoustic voice observation alerted of the case which led to the analysis of the environmental conditions which confirmed the relationship between multiple chemical hypersensitivity and chronic fatigue syndrome. This case stresses the neglected fact that all health service centres pose a high risk of chemical exposure and that there exists a lack of rigoroursness in putting in practice scientific medical knowledge.

 

Source: Arnold Llamosas PA, Arrizabalaga Clemente P, Bonet Agusti M, de la Fuente Brull X. Multiple chemical sensitivity in sick-building syndrome. Med Clin (Barc). 2006 May 27;126(20):774-8. [Article in Spanish] https://www.ncbi.nlm.nih.gov/pubmed/16883665

 

Oxidative stress levels are raised in chronic fatigue syndrome and are associated with clinical symptoms

Abstract:

The aetiology of chronic fatigue syndrome (CFS) is unknown; however, recent evidence suggests excessive free radical (FR) generation may be involved. This study investigated for the first time levels of 8-iso-prostaglandin-F(2 alpha)-isoprostanes alongside other plasma markers of oxidative stress in CFS patients and control subjects.

Forty-seven patients (18 males, 29 females, mean age 48 [19–63] years) who fulfilled the Centres for Disease Control classification for CFS and 34 healthy volunteers (13 males, 21 females, 46 [19–63] years) were enrolled in the study. The CFS patients were divided into two groups; one group had previously defined cardiovascular (CV) risk factors of obesity and hypertension (group 1) and the second were normotensive and nonobese (group 2). Patients had significantly increased levels of isoprostanes (group 1, P=0.007; group 2, P=0.03, unpaired t test compared to controls) and oxidised low-density lipoproteins (group 2, P=0.02) indicative of a FR attack on lipids. CFS patients also had significantly lower high-density lipoproteins (group 1, P=0.011; group 2, P=0.005).

CFS symptoms correlated with isoprostane levels, but only in group 2 low CV risk CFS patients (isoprostanes correlated with; total symptom score P=0.005; joint pain P=0.002; postexertional malaise P=0.027, Pearson). This is the first time that raised levels of the gold standard measure of in vivo oxidative stress (isoprostanes) and their association with CFS symptoms have been reported.

 

Source: Kennedy G, Spence VA, McLaren M, Hill A, Underwood C, Belch JJ. Oxidative stress levels are raised in chronic fatigue syndrome and are associated with clinical symptoms. Free Radic Biol Med. 2005 Sep 1;39(5):584-9. http://www.ncbi.nlm.nih.gov/pubmed/16085177

 

Stress-associated changes in the steady-state expression of latent Epstein-Barr virus: implications for chronic fatigue syndrome and cancer

Abstract:

Antibodies to several Epstein-Barr virus (EBV)-encoded enzymes are observed in patients with different EBV-associated diseases. The reason for these antibody patterns and the role these proteins might play in the pathophysiology of disease, separate from their role in virus replication, is unknown.

In this series of studies, we found that purified EBV deoxyuridine triphosphate nucleotidohydrolase (dUTPase) can inhibit the replication of human peripheral blood mononuclear cells in vitro and upregulate the production of TNF-alpha, IL-1beta, IL-6, IL-8, and IL-10. It also enhanced the ability of natural killer cells to lyse target cells. The EBV dUTPase also significantly inhibited the replication of mitogen-stimulated lymphocytes and the synthesis of IFN-gamma by cells isolated from lymph nodes and spleens obtained from mice inoculated with the protein.

It also produced sickness behaviors known to be induced by some of the cytokines that were studied in the in vitro experiments. These symptoms include an increase in body temperature, a decrease in body mass and in physical activity.

The data provide a new perspective on how an early nonstructural EBV-encoded protein can cause immune dysregulation and produce clinical symptoms observed in patients with chronic fatigue syndrome (CFS) separate from its role in virus replication and may serve as a new approach to help identify one of the etiological agents for CFS. The data also provide additional insight into the pathophysiology of EBV infection, inflammation, and cancer.

 

Source: Glaser R, Padgett DA, Litsky ML, Baiocchi RA, Yang EV, Chen M, Yeh PE, Klimas NG, Marshall GD, Whiteside T, Herberman R, Kiecolt-Glaser J, Williams MV. Stress-associated changes in the steady-state expression of latent Epstein-Barr virus: implications for chronic fatigue syndrome and cancer. Brain Behav Immun. 2005 Mar;19(2):91-103. http://www.ncbi.nlm.nih.gov/pubmed/15664781

 

Childhood predictors of self reported chronic fatigue syndrome/myalgic encephalomyelitis in adults: national birth cohort study

Abstract:

OBJECTIVE: To study childhood risk factors for chronic fatigue syndrome in adult life.

DESIGN: Examination of data from the 1970 British birth cohort.

PARTICIPANTS: 16,567 babies born 5-11 April 1970, followed up at 5, 10, 16, and 29-30 years.

MAIN OUTCOME MEASURES: Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) identified by self report at age 30 years. Data from childhood from questionnaires given to parents and teachers. Maternal mental health assessed with the malaise inventory.

RESULTS: 93 (0.8%, 95% confidence interval 0.7 to 1.0) of 11 261 participants reported ever having CFS/ME, and 48 (0.4%, 0.3 to 0.6) had the condition currently. Higher risk of CFS/ME was associated with having a limiting longstanding condition in childhood (odds ratio 2.3, 1.4 to 3.9), female sex (2.3, 1.4 to 2.6), and high social class in childhood (2.2, 1.4 to 3.5). Higher levels of exercise in childhood were associated with lower risk (0.5, 0.2 to 0.9). Maternal psychological disorder, psychological problems in childhood, birth weight, birth order, atopy, obesity, school absence, academic ability, and parental illness were not associated with risk of CFS/ME.

CONCLUSIONS: We identified no association between maternal or child psychological distress, academic ability, parental illness, atopy, or birth order and increasing risk of lifetime CFS/ME. Sedentary behaviour increased the risk.

Comment in: What causes chronic fatigue syndrome? [BMJ. 2004]

 

Source: Viner R, Hotopf M. Childhood predictors of self reported chronic fatigue syndrome/myalgic encephalomyelitis in adults: national birth cohort study. BMJ. 2004 Oct 23;329(7472):941. Epub 2004 Oct 6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC524102/ (Full article)

 

 

Detection of antibody against Borna disease virus-p24 in the plasma of Chinese patients with chronic fatigue syndrome by Western-blot analysis

Abstract:

OBJECTIVE: To evaluate the prevalence of infection with Borna disease virus (BDV) in Chinese patients with chronic fatigue syndrome (CFS) and control subjects, and to discuss the etiological association between CFS and infection with BDV.

METHODS: The CDC (1994) diagnostic criteria for CFS were used for case definition. Sixty-one patients suffered from CFS were from 11 Provinces in China. To detect the antibody against BDV-p24 on the plasma samples from all cases and 73 healthy control subjects by Western-blotting analysis.

RESULTS: 7 of the sixty-one cases and 0 of the controls were sero-positive for BDV-p24 antibody, there was a statistical significant difference between the two groups (11.48% vs 0%; P less than 0.010).

CONCLUSION: Chinese patients with CFS showed sero-positive identifying BDV infection, by comparison, anti.BDV-p24 antibody prevalence in patients was significantly higher than in controls. An etiological association may exist between CFS and BDV infection.

 

Source: Li YJ, Wang DX, Zhang FM, Liu ZD, Yang AY, Ykuta K. Detection of antibody against Borna disease virus-p24 in the plasma of Chinese patients with chronic fatigue syndrome by Western-blot analysis. Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi. 2003 Dec;17(4):330-3. [Article in Chinese] http://www.ncbi.nlm.nih.gov/pubmed/15340544

 

Electrodermal dissociation of chronic fatigue and depression: evidence for distinct physiological mechanisms

Abstract:

Chronic fatigue syndrome (CFS) has an estimated prevalence between 0.5% and 3%, yet its diagnosis remains contentious. CFS is characterized by subjective symptoms that can be difficult to verify; moreover, depression is a commonly reported CFS complaint, whereas fatigue is a common symptom of depression.

Our primary goal was dissociation of these disorders using psychophysiological methods. As previous research has implicated the autonomic nervous system in CFS, we conducted what we believe to be the first analysis of bilateral electrodermal and skin temperature responses of dextral females in a cross-modal orienting task, to investigate differences between these two patient groups and controls.

A multivariate analysis of variance (MANOVA) examining three measures of electrodermal activity revealed prestimulus tonic skin conductance levels (SCLs) were markedly lower for the CFS group, with no difference between controls and depressives. Concurrent skin temperature levels were higher for the CFS group than the other two groups.

These findings indicate that, despite overtly similar cognitive and symptom profiles, depression and CFS patients can be differentiated with psychophysiological measures. This study adds to the growing body of evidence demonstrating that CFS and depression have distinct neurobiological profiles, consistent with unique aetiologies.

Copyright 2004 Elsevier B.V.

 

Source: Pazderka-Robinson H, Morrison JW, Flor-Henry P. Electrodermal dissociation of chronic fatigue and depression: evidence for distinct physiological mechanisms. Int J Psychophysiol. 2004 Aug;53(3):171-82. http://www.ncbi.nlm.nih.gov/pubmed/15246671